Mass spectrometry (MS) is an analytical technique utilized to produce spectra of the masses of ions produced from molecules of a sample of interest. The obtained spectra of masses are utilized to identify the molecules in the sample by correlating the measured masses with the known masses of ions associated with specific molecules. In a typical MS instrument, a sample is ionized, and the produced ions are subsequently separated in a mass analyzer according to their mass-to-charge ratio. The ions are detected by a mechanism capable of detecting charged particles (an ion detector), and the derived signal is displayed as a spectrum of the relative abundance of ions as a function of their mass-to-charge ratios (or m/z values, or more simply “masses”).
Tandem mass spectrometry (MS-MS) is an analytical technique that utilizes multiple stages of mass spectrometry, which are usually separated by some form of ion fragmentation device such as a collision cell. MS-MS can be utilized to produce structural information about a compound by fragmenting specific ions inside the mass spectrometer and identifying the resulting fragment ions. This information can then be pieced together to generate structural information about the intact molecule. A typical tandem mass spectrometer has two mass analyzers separated by a collision cell into which an inert gas (e.g., argon, nitrogen) is admitted to collide with the selected sample of ions, causing the desired fragmentation. The mass analyzers can be of the same or different types, the most common combinations being quadrupole-quadrupole and quadrupole-time-of-flight.
In typical applications of MS-MS, the sample of the material to be analyzed is a complex mixture of many distinct molecular species. The first mass analyzer stage is used to select a range of ion masses to transmit to the collision cell for fragmentation. Conventionally, this first stage is required to transmit only a limited number of molecular species (“precursor” or “parent” ions) so that after fragmentation the resulting mass spectrum (“product” or “daughter” ions) is simple enough that daughter mass peaks can be identified with the correct parent ion. Clearly, if many different species of parent ions were transmitted through the first mass analyzer and subsequently passed through the collision cell, the resulting spectrum of daughter ions appearing at the final mass analyzer stage would have a complexity that would preclude this identification.
This requirement that the first mass analyzer stage in MS-MS applications pass only a limited range of mass-to-charge ratios at a given time can be an undesirable restriction. Specifically, when the MS-MS system is being utilized in tandem with a real-time analytical separation process such as a chromatographic separation process, the chromatographic time-scale may not allow sufficient time for the MS-MS system to step through the many (narrow) mass windows required to adequately analyze the eluting sample material at a particular time. A related problem is that most of the ions entering the MS-MS system do not make it past the first mass analyzer stage as the full mass range is scanned with a narrow mass window. This has a negative impact on abundance sensitivity in applications where there is limited access time to a particular sample, or the total amount of available sample is small.
To mitigate these restrictions, there is a need for methods and apparatuses that would allow a greater fraction of the ions to pass through the first mass analyzer stage at any given time, and still allow the complex spectrum of daughter ions to be disentangled, and uniquely identify daughter ion peaks with the correct parent ion.